What are SNPs?

SNP (pronounced "snip") stands for single nucleotide polymorphism. Polymorphism refers to the presence of more than one allele of a gene in a population. This allele must be present in more than 1% of the population to distinguish it from a mutation. A SNP is a specific type of allele caused by a small genetic change, or variation, that occurred generations ago within a DNA sequence. The replacement of one single nucleotide with any one of the other three nucleotides resulted in a SNP. A SNP is, therefore, the simplest kind of polymorphism because it involves only one nucleotide change.

The following is one example of a mutation that may have occurred over evolutionary time, persisted, and resulted in a SNP. Originally, one DNA segment on a chromosome reads GGTAAC. The replacement of the second G with a C created a novel DNA segment that reads GCTAAC. This variation is referred to as a G/C SNP. Each individual in the population inherits a version of the SNP on the chromosome donated from each parent. Therefore, each SNP variant that occurs at a particular site on a chromosome is shared by some fraction of the population.

There are probably five to 10 million SNPs in the human genome and it is estimated that about 60,000 of them are found within regions of DNA that code for proteins. Because codons are like words made of three nucleotides (or letters), a single nucleotide change in the DNA sequence of a chromosome alters the codon at that site. The new codon has the potential to direct the cell's machinery to add a different amino acid at this site during protein synthesis. The substituted amino acid may alter either the protein's stability or function. In this manner, SNPs may be responsible for many of the phenotypic differences between humans. The majority of SNPs, however, occur in noncoding regions of the DNA and are not responsible for any protein changes.

How Are SNPs Being Used?

SNPs are being identified that serve as genetic markers for disease. In order to establish a link between a SNP and a specific disease, the genomes of many different individuals need to be scanned for SNPs. Several SNPs are identified within the individual and a SNP profile is constructed. The identified SNPs are also recorded in web-based databases. To determine whether a particular SNP is associated with a disease, the frequency of the SNP pattern found in individuals affected with a disease is compared to the SNP pattern found in unaffected individuals. A SNP may confer disease susceptibility if one pattern is found to be significantly more common in the affected population than in the control group. In some cases, a disease-linked SNP has been identified and a screening test for the disease based on the SNP has been developed. Information about an individual's SNP profile may indicate whether one is at an increased risk, for example, of developing heart disease. The individual may then be able to modify their lifestyle or take medications to prevent the disease rather than waiting for symptoms to occur. However, a SNP profile could also identify other diseases, such as Huntington's, for which there is no effective prevention or treatment. It is important to note that although SNPs may serve as genetic markers for a disease, the majority are not responsible for causing the disease.

It may theoretically become possible to scan one's entire genome for all SNPs. A complete genome SNP profile could indicate a whole range of diseases to which one is predisposed. Currently, the cost of sequencing every individual's genome is prohibitive. However, as Glyn Moody, author of Digital Code of Life: How Bioinformatics is Revolutionizing Science, Medicine, and Business, writes, "with a dozen companies racing towards the goal of the sub-$1000 genome, the day when your DNA is sequenced and burnt on to a CD-ROM for roughly the cost of a conventional health checkup is not far off" (The Guardian, April 15, 2004).

SNP profiles can be used in medicine beyond identifying disease risk. One hot area in pharmaceutical research is the design of personalized drug treatments based on a patient's SNP profile. SNP information could allow drug therapy to be customized. Individuals always vary in their response to medication both in terms of effectiveness and side effects. SNPs may provide information about the most appropriate drug to prescribe or the optimal dose. One example is the SNP that occurs in the morphine receptor. Individuals homozygous for one SNP allele are known to need much higher levels of morphine-derived pain relieving drugs. Development of a SNP screening test will allow treatment of those individuals with the appropriate dose of morphine.

In addition to medical uses, SNPs are proving useful in mapping the migrations of human populations. SNPs provide information about human evolution and the descent from ancestral populations (see, for example, "Who Were the Phoenicians?" in the October 2004 issue of National Geographic Magazine).